Serum midkine levels for the diagnosis and assessment of response to interventional therapy in patients with hepatocellular carcinoma

Objective

To explore the clinical significance of serum midkine (MDK) levels for the diagnosis of hepatocellular carcinoma (HCC) and evaluate the efficacy of interventional therapy.

Methods

Eighty-four patients with HCC were enrolled in this retrospective study. They received an interventional treatment. A follow-up was performed every 2 months, using magnetic resonance imaging, to determine whether the treatment should be continued. Serum alpha-fetoprotein (AFP) and MDK levels were measured at the first diagnosis and during the follow-ups, and the HCC detection rates based on the cutoff values of these two measurements were compared. The relationships between AFP and MDK and the clinical tumor characteristics and changes in APK and MDK before and after treatment were also compared using a rank sum test and χ² test, respectively. The prognostic significance of MDK for HCC was determined through regression analysis. A two-sided P ​< ​0.05 was considered statistically significant.

Results

MDK expression was detected in 95.24% of the cases. Subgroup analysis revealed MDK expression in 95.35%, 95.12%, 85.19%, 86.67%, and 83.33% of the AFP-positive, AFP-negative, stage A Barcelona clinic liver cancer (BCLC-A), BCLC-A/AFP-positive, and BCLC-A/AFP-negative cases, respectively. MDK expression after the interventional treatment (66.7%) was significantly lower than that before the treatment (95.2%). The mean post-treatment MDK level was 0.67 ​ng/mL in patients with a positive response to therapy as compared with 3.66 ​ng/mL in those with no positive response. All patients were followed up for 18 months, and those positive for MDK expression before the intervention were more likely to relapse than patients without MDK expression. Subgroup analysis revealed the highest recurrence rate for patients who were positive for MDK expression before and after treatment.

Conclusions

Serum MDK may serve as a powerful complement to AFP in the diagnosis of HCC. MDK measurement may improve the detection rate of BCLC-A and AFP-negative HCC. Serum MDK may help to determine the vascular invasion and poor clinical staging of HCC tumors. Patients with MDK-positive HCC before treatment may be more prone to postoperative tumor progression.